Arthritis and Rheumatism

Recent data have shown that abnormal subchondral bone remodeling plays an important role in osteoarthritis (OA) onset and progression, and it was suggested that abnormal mechanical pressure applied to the articulation was responsible for these metabolic changes. This study was undertaken to evaluate the effects of cyclic compression on osteoblasts from OA subchondral bone.Osteoblasts were isolated from sclerotic and nonsclerotic areas of human OA subchondral bone. After 28 days, the osteoblasts were surrounded by an abundant extracellular matrix and formed a resistant membrane, which was submitted to cyclic compression (1 MPa at 1 Hz) for 4 hours. Gene expression was evaluated by reverse transcription-polymerase chain reaction. Protein production in culture supernatants was quantified by enzyme-linked immunosorbent assay or visualized by immunohistochemistry.Compression increased the expression of genes coding for interleukin-6 (IL-6), cyclooxygenase 2, RANKL, fibroblast growth factor 2, IL-8, matrix metalloproteinase 3 (MMP-3), MMP-9, and MMP-13 but reduced the expression of osteoprotegerin in osteoblasts in both sclerotic and nonsclerotic areas. Colα1(I) and MMP-2 were not significantly affected by mechanical stimuli. Nonsclerotic osteoblasts were significantly more sensitive to compression than sclerotic ones, but after compression, differences in messenger RNA levels between nonsclerotic and sclerotic osteoblasts were largely reduced or even abolished. Under basal conditions, sclerotic osteoblasts expressed similar levels of α5, αv, β1, and β3 integrins and CD44 as nonsclerotic osteoblasts but 30% less connexin 43, an important mechanoreceptor.Genes involved in subchondral bone sclerosis are mechanosensitive. After compression, nonsclerotic and sclerotic osteoblasts expressed a similar phenotype, suggesting that compression could be responsible for the phenotype changes in OA subchondral osteoblasts.

Christelle Sanchez

Laurence Pesesse

Odile Gabay

Jean‐Pierre Delcour

Philippe Msika

Caroline Baudouin

Yves E. Henrotin

Arthritis & Rheumatism

Regulation of subchondral bone osteoblast metabolism by cyclic compression

Abstract Objective The receptor for advanced glycation end products (RAGE) binds multiple ligands, including S100 proteins, high mobility group box chromosomal protein 1 (HMGB‐1), and AGEs, all of which are present in articular cartilage. Stimulation of RAGE signaling can lead to MAP kinase activation and increased NF‐κB activity. The objective of the present study was to determine if chondrocytes express functional RAGE. Methods The presence of chondrocyte RAGE was analyzed by immunohistochemistry using normal and osteoarthritic (OA) cartilage from young and old monkeys and humans, immunoblotting of chondrocyte lysates and human cartilage extracts, and reverse transcription–polymerase chain reaction (RT‐PCR) analysis of RNA from chondrocytes treated with interleukin‐1 (IL‐1) and fibronectin fragments. RAGE signaling was evaluated by stimulating chondrocytes with S100B and HMGB‐1 and analyzing for activation of the ERK MAP kinase and NF‐κB. The ability of S100B and HMGB‐1 to stimulate matrix metalloproteinase 13 (MMP‐13) production was also assessed. A pull‐down assay using biotin‐labeled S100B was used to demonstrate binding to RAGE. Results RAGE was detected in sections of monkey knee cartilage and human knee and ankle cartilage. Increased immunostaining for RAGE was noted in cartilage from older adult monkeys and humans and was further increased in OA tissue. RAGE was also detected by immunoblotting and by RT‐PCR, where IL‐1β and fibronectin fragments were found to stimulate RAGE expression. Stimulation of chondrocytes with S100B or HMGB‐1 increased phosphorylation of the ERK MAP kinase and the p65 subunit of NF‐κB and increased the production of MMP‐13. This signaling was inhibited in cells pretreated with soluble RAGE, and S100B was shown to bind to chondrocyte RAGE. Conclusion Articular chondrocytes express functional RAGE. The increase in RAGE noted in OA cartilage and the ability of RAGE ligands to stimulate chondrocyte MAP kinase and NF‐κB activity and to stimulate MMP‐13 production suggests that chondrocyte RAGE signaling could play a role in OA.

Richard F. Loeser

Raghunatha R. Yammani

Cathy S. Carlson

Hong Chen

Ada Cole

Hee‐Jeong Im

Laura S. Bursch

Shi Du Yan

Articular chondrocytes express the receptor for advanced glycation end products: Potential role in osteoarthritis

关节软骨细胞表达晚期糖基化终末产物受体：在骨关节炎中的潜在作用

To investigate the role of cytokines and growth factors in the regulation of hyaluronan synthesis in human synovial lining cells.Synovial lining cells were obtained from human knee joints, isolated by the explant method, and characterized by immunocytochemistry using monoclonal antibodies against monocyte/macrophage markers as well as antibodies against hyaluronan synthase. After stimulation by cytokines and growth factors, hyaluronan was measured by radiometric assay. The molecular weight distribution of the hyaluronan synthesized was determined by high-performance gel-permeation liquid chromatography. To test the effect of oxygen-derived free radicals, the concentration and molecular weight distribution of hyaluronan were determined in the presence and absence of catalase and superoxide dismutase.Hyaluronan synthesis was stimulated in synovial lining cells by transforming growth factor beta 1 (TGF beta 1), interleukin-1 beta (IL-1 beta), and to a lesser extent by tumor necrosis factor alpha (TNF alpha). Analysis of the molecular weight distribution of hyaluronan after stimulation of synovial lining cells with TGF beta 1, IL-1 beta, and TNF alpha indicated that hyaluronan is synthesized in a high molecular weight form and might be degraded in the course of inflammatory processes by oxygen-derived free radicals.Our findings suggest that TGF beta 1 is a major stimulator of hyaluronan synthesis in human synovial lining cells and might be involved in the pathogenic mechanisms of joint swelling in inflammatory and degenerative joint diseases.

Hans‐Dieter Haubeck

RÜDiger Kock

Dagmar‐Christiane Fischer

Eddy Van De Leur

Karin Hoffmeister

Helmut Greiling

Transforming growth factor β1, a major stimulator of hyaluronan synthesis in human synovial lining cells

转化生长因子β1是人滑膜衬里细胞透明质酸合成的主要刺激因子

Abstract Objective To determine whether interleukin‐1 (IL‐1) or tumor necrosis factor α (TNFα), or both, plays a role in the excessive degradation that is observed in cultured osteoarthritic (OA) articular cartilage. Methods Antagonists of IL‐1 and TNFα, namely, IL‐1 receptor antagonist and the PEGylated soluble TNFα receptor I, respectively, were added at different concentrations to explant cultures of nonarthritic (5 obtained at autopsy) and OA (15 obtained at arthroplasty) articular cartilage. The cleavage of type II collagen (CII) by collagenase was measured by an immunoassay in cartilage and culture media. Proteoglycan (mainly aggrecan) content and degradation were measured by a colorimetric assay for glycosaminoglycan (GAG) content in cartilage and culture media. Reverse transcriptase–polymerase chain reaction was used to analyze gene expression of matrix metalloproteases (MMPs) 1, 3, and 13, CII, aggrecan, IL‐1, and TNFα. Results Antagonists of IL‐1 and TNFα inhibited the increase in CII cleavage by collagenase as well as the increase in GAG release observed in OA cartilage compared with normal cartilage. Inhibition was significant in tissue from some patients but not from others, although significant inhibition was observed when all the results were analyzed together. An increase in the GAG content in cartilage was seen in 4 of 15 cases. However, this increase was not significant when all the data were combined. Preliminary results indicated no effect of these antagonists on nonarthritic cartilage from 3 different donors. Independent analyses of gene expression in cultured cartilage from 9 other OA patients revealed that IL‐1 or TNFα blockade, either alone and/or in combination, frequently down‐regulated MMP‐1, MMP‐3, and MMP‐13 expression. Expression of IL‐1 and TNFα was inhibited by either antagonist or by the combination in essentially half the cases. The combined blockade up‐regulated aggrecan and CII gene expression in approximately half the cases. Conclusion These results suggest that the autocrine/paracrine activities of TNFα and IL‐1 in articular cartilage may play important roles in cartilage matrix degradation in OA patients but not in all patients. Inhibition of either or both of these cytokines may offer a useful therapeutic approach to the management of OA by reducing gene expression of MMPs involved in cartilage matrix degradation and favoring its repair.

Masahiko Kobayashi

Ginette R. Squires

Aisha Mousa

Michael Tanzer

David J. Zukor

John Antoniou

Ulrich Feige

A. Robin Poole

Role of interleukin‐1 and tumor necrosis factor α in matrix degradation of human osteoarthritic cartilage

人骨关节炎软骨基质降解中白细胞介素-1和肿瘤坏死因子α的作用

Abstract Objective Although knee malalignment is assumed to correlate with knee osteoarthritis (OA), it is still unknown whether malalignment precedes the development of OA or whether it is a result of OA. The aim of this study was to assess the relationship between malalignment and the development of knee OA as well as progression of knee OA. Methods A total of 1,501 participants in the Rotterdam study were randomly selected. Knee OA at baseline and at followup (mean followup 6.6 years) was scored according to the Kellgren/Lawrence (K/L) grading system. Alignment was measured by the femorotibial angle on radiographs at baseline. Multivariable logistic regression for repeated measurements was used to analyze the association of malalignment with the development and progression of OA. Results Of 2,664 knees, 1,012 (38%) were considered to have normal alignment, 693 (26%) had varus alignment, and 959 (36%) had valgus alignment. A comparison of valgus alignment and normal alignment showed that valgus alignment was associated with a borderline significant increase in development of knee OA (odds ratio [OR] 1.54, 95% confidence interval [95% CI] 0.97–2.44), and varus alignment was associated with a 2‐fold increased risk (OR 2.06, 95% CI 1.28–3.32). Stratification for body mass index showed that this increased risk was especially seen in overweight and obese individuals but not in non‐overweight persons. The risk of OA progression was also significantly increased in the group with varus alignment compared with the group with normal alignment (OR 2.90, 95% CI 1.07–7.88). Conclusion An increasing degree of varus alignment is associated not only with progression of knee OA but also with development of knee OA. However, this association seems particularly applicable to overweight and obese persons.

G. M. Brouwer

A. W. Van Tol

A. P. Bergink

J. N. Belo

R. M. D. Bernsen

M. Reijman

H. A. P. Pols

S. M. A. Bierma‐Zeinstra

Association between valgus and varus alignment and the development and progression of radiographic osteoarthritis of the knee

膝内翻和外翻对膝关节放射学骨关节炎发生和进展的关联

Peter Grayson

Cristina Ponte

Ravi Suppiah

Joanna C Robson

Anthea Craven

Andrew Judge

Sara Khalid

Andrew Hutchings

Raashid Luqmani

Richard Watts

Peter Merkel

2021 American College of Rheumatology /European League Against Rheumatism Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis

2021年美国风湿病学会/欧洲抗风湿病联盟嗜酸性肉芽肿性多血管炎分类标准

Publication Information	Publisher: John Wiley & Sons Inc.，Publishing cycle: Monthly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 1958，Proportion of original research papers: 0.00%，Self Citation Rate:N.A.， Gold OA Rate: 0.00%
Average review cycle	网友分享经验：平均1月
Average recruitment ratio	网友分享经验：约25%

Arthritis and Rheumatism

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Regulation of subchondral bone osteoblast metabolism by cyclic compression

Articular chondrocytes express the receptor for advanced glycation end products: Potential role in osteoarthritis

Transforming growth factor β1, a major stimulator of hyaluronan synthesis in human synovial lining cells

Role of interleukin‐1 and tumor necrosis factor α in matrix degradation of human osteoarthritic cartilage

Association between valgus and varus alignment and the development and progression of radiographic osteoarthritis of the knee

2021 American College of Rheumatology /European League Against Rheumatism Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis

2021 American College of Rheumatology /European League Against Rheumatism Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis

2021 American College of Rheumatology /European League Against Rheumatism Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis

2021 American College of Rheumatology /European League Against Rheumatism Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis

2021 American College of Rheumatology /European League Against Rheumatism Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis